Cultured normal human and animal cells have a limited replicative capacity (Phase III). The number of population doublings traversed is inversely proportional to donor age and directly proportional to species mean lifespan. For example, human embryo fibroblasts have a replicative capacity of 50 plus or minus 10 population doublings. This finitude of normal cell proliferation has also been demonstrated to occur in vivo. The Phase III phenomenon first described by us twelve years ago, is interpreted to be a manifestation of biological aging at the cell level. The cessation of mitotic or functional capacity is best explained by specific genetic programming or accumulation of mis-specified macro-molecules. Studies will be directed toward testing these notions by: (1) mass cell enucleation-hybridization techniqes, (2) longitudinal and cross-sectional determination of the university of the Phase III phenomenon, (3) cell doubling kinetics including pedigree and interdivision time analysis, (4) clonal and cohort analysis and (5), study of the Phase III phenomenon in epithelial cells derived from various human and animal tissues.